The brain capillary endothelium is the main constituent of the blood-brain barrier. This study demonstrates that various vasoconstrictive peptides evoke dissimilar responses in the endothelial cells derived from human brain (HBEC) and human umbilical vein (HUVEC). Samples of human brain surgically removed for the treatment of idiopathic epilepsy served for isolation of HBEC, whereas HUVEC were obtained commercially. Both types of cells were characterized as endothelium (>98%) by positive staining for Factor VIII-related antigen and negative staining for GFAP and other non- endothelial markers. Vasoconstrictive peptides [endothelin-1 (ET-1), arginine-vasopressin (AVP), angiotensin II (Ang II)] markedly stimulated a transient (1-15 min) increase in IP3 formation [EC50 (ET-1<AVP<Ang II)] in HBEC, while only Ang II was slightly effective on HUVEC. All three peptides also increased release of arachidonic acid (AA) from HBEC, but not from HUVEC. Both peptide-stimulated IP3 and AA release in HBEC were inhibited by selective peptide receptor antagonists indicating the presence of ETA, V1, and Ang II receptors on HBEC. In contrast, HBEC reactivity to histamine was similar to that of HUVEC and consistent with the presence of histamine H1 receptors on both cell types. ET-1 (10-100 nM) increased the release of 51Cr (8.2% vs. 15.7%), but not lactate dehydrogenase in HBEC only, while histamine was ineffective on either cell type. The distinct biochemical properties of EC derived from different tissues strongly suggest that these cells may be involved in the regionally diverse functions of vessels.